Principal Findings:

Time to angina was 51 seconds longer with ranolazine versus placebo (p<0.001) and 39.5 seconds longer with atenolol versus placebo (p<0.001). Time to angina with ranolazine was 11.4 seconds longer than atenolol, although the difference was not statistically significant (p=0.18). Increase in exercise duration was also longer with both ranolazine and atenolol versus placebo (37.1 seconds [p<0.001] and 16.0 seconds [p<0.04], respectively), while ranolazine was also longer than atenolol (21.1 seconds, p=0.006). Time to ST depression was longer with both ranolazine and atenolol versus placebo (52.6 seconds and 51.0 seconds, respectively, p<0.001 for each), but there was no difference between the two active therapies (p=0.86).

Blood pressure and heart rate at rest and at maximal exercise were significantly lower with atenolol compared with ranolazine and placebo. There was no significant difference in blood pressure or heart rate at rest, or in heart rate at maximal exercise for ranolazine compared with placebo. However, systolic blood pressure at maximal exercise was slightly but significantly higher for ranolazine compared with placebo (184 mm Hg vs. 179 mm Hg, p<0.05).

Cardiac work as measured by rate-pressure product was significantly lower with atenolol compared to placebo or ranolazine both at rest and at maximal exercise. There was no difference between ranolazine and placebo in cardiac work by rate-pressure product.

Adverse events were reported in 29% of patients during the ranolazine phase, 25% during the atenolol phase, and 17% during the placebo phase. There were no significant changes observed in QTc, PR, or QRS intervals.